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影响人脑胶质瘤细胞发生、增殖关键lncRNA、miRNA的筛选与分析
Screening and Analysis of Key lncRNA and miRNA Affecting the Occurrence and Proliferation of Human Glioma Cells

DOI: 10.12677/ACRPO.2021.101001, PP. 1-23

Keywords: 胶质瘤，lncRNA，miRNA，ceRNA网络，联合分析
Glioma, lncRNA, miRNA, ceRNA Network, Conjoint Analysis

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Abstract:

脑胶质瘤是一种极度常见颅腔内的原发性恶性肿瘤，患病人群占据所有颅内肿瘤患者的60%。IV级胶质瘤为最高恶性程度，也称为胶质母细胞瘤(胶质母细胞瘤，GBM)，约占全部胶质瘤的55%，且诊断为GBM的患者5年生存率低于6%。许多研究表明，脑胶质瘤中异常表达的lncRNA不仅调控着与癌细胞增殖、凋亡有关的信号转导通路，还与病人的预后有关。利用转录组高通量测序方法，筛选影响脑胶质瘤发生、发展及复发过程中关键通路中的重要基因，对脑胶质瘤的分子诊断、靶向药物的研发及新治疗方案的选择具有重要的价值。本研究通过RNA-seq和生物信息学分析，筛选出在脑胶质瘤组织中差异表达的lncRNA 106种，其中上调表达52种，下调表达54种。microRNA共计15个，其中上调表达8种；下调表达7种。这些差异表达的ncRNA主要参与有机循环化合物代谢过程、胞内运输、细胞蛋白质定位、蛋白质运输、有丝分裂细胞周期、细胞周期调节、DNA代谢过程的正调控、水解酶活性的调节等生物过程、生物调节、应激反应、多细胞有机体过程、细胞成分的组织或生物发生、细胞定位、信号途径、发育过程、生物过程的正调控与负调控。经lncRNA-miRNA-mRNA关联分析，建立了ceRNAs调控网络，明确了lncRNA、miRNA与靶标mRNA之间的对应关系。这些关键lncRNA的筛选，为脑胶质瘤的诊断及治疗提供了新的思路与方向。
Glioma is an extremely common primary malignant tumor in the cranial cavity, which accounts for 60% of all patients with intracranial tumors. Grade IV glioma is the highest degree of malignancy, also called glioblastoma (glioblastoma, GBM), accounting for about 55% of all gliomas, and the 5-year survival rate of patients diagnosed with GBM is lower than 6%. Many studies have shown that the abnormally expressed lncRNA in brain gliomas not only regulates the signal transduction pathways related to cancer cell proliferation and apoptosis, but is also related to the patient’s prognosis. Using transcriptome high-throughput sequencing to screen important genes in key pathways that affect the development, development and recurrence of glioma is of great value for molecular diagnosis of glioma, research and development of targeted drugs and selection of new treatment options. In this study, through RNA-seq and bioinformatics analysis, 106 types of lncRNAs that are differentially expressed in glioma tissues were screened, of which 52 were up-regulated and 54 were down-regulated. There are a total of 15 microRNAs, of which 8 are up-regulated and 7 are down-regulated. These differentially expressed ncRNAs are mainly involved in the metabolic process of organic circulating compounds, intracellular transport, cell protein localization, protein transport, mitotic cell cycle, cell cycle regulation, positive regulation of DNA metabolism, regulation of hydrolase activity and other biological processes and biological regulation, Stress response, multicellular organism process, tissue or biogenesis of cell components, cell location, signal pathway, development process, positive and negative regulation of biological processes. After lncRNA-miRNA-mRNA association analysis, a ceRNAs regulatory network was established, and the correspondence between lncRNA, miRNA and target mRNA was clarified. The screening of these

References

[1]  Rees, J.H. (2011) Diagnosis and Treatment in Neuro-Oncology: An Oncological Perspective. The British Journal of Ra-diology, 84, 82-89.
https://doi.org/10.1259/bjr/18061999
[2]  中华医学会病理学分会脑神经病理学组. 2016 WHO中枢神经系统肿瘤分类第4版修订版概述及胶质瘤部分介绍[J]. 中华病理学杂志, 2016, 45(11): 745-747.
[3]  Muir, C.S., Storm, H.H. and Polednak, A. (1994) Brain and Other Nervous System Tumours. Cancer Survival, 19-20, 369-392.
[4]  中国中枢神经系统胶质瘤诊断与治疗指南编写组. 中华医学杂志[J]. 中华医学会, 2016, 96(7): 485-509.
[5]  Strom, Q.T., Gittleman, H., Liao, P., et al. (2016) CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009-2013. Neuro-Oncology, 18, v1-v75.
https://doi.org/10.1093/neuonc/now207
[6]  Ng, H.K. and Lam, P.Y. (1998) The Molecular Genetics of Central Nervous System Tumors. Pathology, 30, 196-202.
https://doi.org/10.1080/00313029800169236
[7]  Schlessinger, J. (2000) Cell Signaling by Receptor Tyrosine Ki-nases. Cell, 103, 211-225.
https://doi.org/10.1016/S0092-8674(00)00114-8
[8]  王曦, 陈定. LncRNAs作为miRNA的靶模拟物调节miRNA [J]. 科技创新导报, 2016, 13(28): 176-177.
[9]  Marziali, A. and Akeson, M. (2001) New DNA Sequencing Methods. Annual Review of Biomedical Engineering, 3, 195-223.
https://doi.org/10.1146/annurev.bioeng.3.1.195
[10]  Goodwin, S., McPherson, J.D. and McCombie, W.R. (2016) Coming of Age: Ten Years of Next-Generation Sequencing Technologies. Nature Reviews Genetics, 17, 333-351.
https://doi.org/10.1038/nrg.2016.49
[11]  Niedzicka, M., Fijarczyk, A., Dudek, K., et al. (2016) Molecular Inver-sion Probes for Targeted Resequencing in Non-Model Organisms. Scientific Reports, 6, Article No. 24051.
https://doi.org/10.1038/srep24051
[12]  Xu, J., Gao, C., Zhang, F., et al. (2016) Differentially Expressed lncRNAs and mRNAs Identified by Microarray Analysis in GBS Patients vs Healthy Controls. Scientific Reports, 6, Article No. 21819.
https://doi.org/10.1038/srep21819
[13]  Xu, J., Zhang, F., Gao, C., et al. (2017) Microarray Analysis of lncRNA and mRNA Expression Profiles in Patients with Neuromyelitis Optica. Molecular Neurobiology, 54, 2201-2208.
https://doi.org/10.1007/s12035-016-9754-0
[14]  Wang, Z., Gerstein, M. and Snyder, M. (2009) RNA-Seq: A Revolutionary Tool for Transcriptomics. Nature Reviews Genetics, 10, 57-63.
https://doi.org/10.1038/nrg2484
[15]  Yang, Y., et al. (2018) Analyzing the Interactions of mRNAs, miRNAs, lncRNAs and circRNAs to Predict Competing Endogenous RNA Networks in Glioblastoma. Journal of Neu-ro-Oncology, 137, 493-502.
https://doi.org/10.1007/s11060-018-2757-0
[16]  《中国中枢神经系统胶质瘤诊断与治疗指南》编写组. 中华医学杂志[J]. 中华医学会, 2016, 96(7): 485-509.
[17]  Kim, D., Pertea, G., Trapnell, C., et al. (2013) TopHat2: Accurate Alignment of Transcriptomes in the Presence of Insertions, Deletions and Gene Fusions. Genome Biology, 14, R36.
https://doi.org/10.1186/gb-2013-14-4-r36
[18]  Trapnell, C., Williams, B.A., Pertea, G., et al. (2010) Transcript Assembly and Quantification by RNA-Seq Reveals Unannotated Transcripts and Isoform Switching during Cell Differ-entiation. Nature Biotechnology, 28, 511-515.
https://doi.org/10.1038/nbt.1621
[19]  Liang, S., Luo, H., Bu, D., et al. (2013) Utilizing Sequence Intrinsic Compo-sition to Classify Protein-Coding and Long Noncoding Transcripts. Nucleic Acids Research, 41, e166.
https://doi.org/10.1093/nar/gkt646
[20]  Kong, L., Zhang, Y., Ye, Z.Q., et al. (2007) CPC: Assess the Pro-tein-Coding Potential of Transcripts Using Sequence Features and Support Vector Machine. Nucleic Acids Research, 35, W345-W349.
https://doi.org/10.1093/nar/gkm391
[21]  Punta, M., Coggill, P.C., Eberhardt, R.Y., et al. (2011) The Pfam Protein Families Database. Nucleic Acids Research, 40, D290-D301.
https://doi.org/10.1093/nar/gkr1065
[22]  Lin, M.F., Jungreis, I. and Kellis, M. (2011) PhyloCSF: A Comparative Genomics Method to Distinguish Protein Coding and Non-Coding Regions. Bioinformatics, 27, i275-i282.
https://doi.org/10.1093/bioinformatics/btr209
[23]  Young, M.D., Wakefield, M.J., Smyth, G.K., et al. (2010) Gene Ontology Analysis for RNA-seq: Accounting for Selection Bias. Genome Biology, 11, R14.
https://doi.org/10.1186/gb-2010-11-2-r14
[24]  Mao, X., Cai, T., Olyarchuk, J.G., et al. (2005) Automated Genome Annotation and Pathway Identification Using the KEGG Orthology (KO) as a Controlled Vocabulary. Bioinformatics, 21, 3787-3793.
https://doi.org/10.1093/bioinformatics/bti430
[25]  Kanehisa, M., Araki, M., Goto, S., et al. (2008) KEGG for Linking Genomes to Life and the Environment. Nucleic Acids Research, 36, D480-D484.
https://doi.org/10.1093/nar/gkm882
[26]  Yao, L., Ye, P.C., Tan, W., et al. (2020) Decreased Expression of the Long Non-Coding RNA HOXD-AS2 Promotes Gastric Cancer Progression by Targeting HOXD8 and Activating PI3K/Akt Signaling Pathway. World Journal of Gastrointestinal Oncology, 12, 1237-1254.
https://doi.org/10.4251/wjgo.v12.i11.1237
[27]  Zhang, W., Fei, J., Yu, S., et al. (2018) LINC01088 Inhibits Tu-morigenesis of Ovarian Epithelial Cells by Targeting miR-24-1-5p. Scientific Reports, 8, Article No. 2876.
https://doi.org/10.1038/s41598-018-21164-9
[28]  Xue, C., Zhao, Y., Jiang, J. and Li, L. (2020) Expression Levels of lncRNAs Are Prognostic for Hepatocellular Carcinoma Overall Survival. American Journal of Translational Research, 12, 1873-1883.
[29]  O’Brien, H.E., Hannon, E., Hill, M.J., et al. (2018) Expression Quantitative Trait Loci in the De-veloping Human Brain and Their Enrichment in Neuropsychiatric Disorders. Genome Biology, 19, 194.
https://doi.org/10.1186/s13059-018-1567-1
[30]  Deist, M.S., Gallardo, R.A., Bunn, D.A., Dekkers, J.C.M., Zhou, H. and Lamont, S.J. (2017) Resistant and Susceptible Chicken Lines Show Distinctive Responses to Newcastle Disease Virus Infection in the Lung Transcriptome. BMC Genomics, 18, 989.
https://doi.org/10.1186/s12864-017-4380-4
[31]  Rathe, S.K., Popescu, F.E., Johnson, J.E., et al. (2019) Identifica-tion of Candidate Neoantigens Produced by Fusion Transcripts in Human Osteosarcomas. Scientific Reports, 9, Article No. 358.
https://doi.org/10.1038/s41598-018-36840-z
[32]  Pande, M., Joon, A., Brewster, A.M., et al. (2018) Genetic Sus-ceptibility Markers for a Breast-Colorectal Cancer Phenotype: Exploratory Results from Genome-Wide Association Studies. PLoS ONE, 13, e0196245.
https://doi.org/10.1371/journal.pone.0196245
[33]  Liu, J.Q., Feng, Y.H., Zeng, S. and Zhong, M.Z. (2020) linc01088 Promotes Cell Proliferation by Scaffolding EZH2 and Repressing p21 in Human Non-Small Cell Lung Cancer. Life Sciences, 241, Article ID: 117134.
https://doi.org/10.1016/j.lfs.2019.117134
[34]  Ai, H., Xie, W., Xiu, A.H., et al. (2018) The Down-Regulation of Long Non-Coding RNA LINC01088 Is Associated with the Poor Prognosis of Epithelial Ovarian Cancer Patients. Eu-ropean Review for Medical and Pharmacological Sciences, 22, 5836-5841.
[35]  Liu, J., Yao, Y., Hu, Z., Zhou, H. and Zhong, M. (2019) Transcriptional Profiling of Long-Intergenic Noncoding RNAs in Lung Squamous Cell Carcinoma and Its Value in Diagnosis and Prognosis. Molecular Genetics & Genomic Medicine, 7, e994.
https://doi.org/10.1002/mgg3.994
[36]  Kasiviswanathan, D., Chinnasamy Perumal, R., Bhuvaneswari, S., et al. (2020) Interactome of miRNAs and Transcriptome of Human Umbilical Cord Endothelial Cells Exposed to Short-Term Simulated Microgravity. NPJ Microgravity, 6, 18.
https://doi.org/10.1038/s41526-020-00108-6
[37]  Liao, B., Zhou, M.X., Zhou, F.K., et al. (2020) Exosome-Derived MiRNAs as Biomarkers of the Development and Progression of In-tracranial Aneurysms. Journal of Atherosclerosis and Thrombosis, 27, 545-610.
https://doi.org/10.5551/jat.51102
[38]  Zhao, H., et al. (2020) Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer. Disease Markers, 2020, Article ID: 2860582.
https://doi.org/10.1155/2020/2860582
[39]  Motti, M.L., Minopoli, M., Di Carluccio, G., Ascierto, P.A. and Carri-ero, M.V. (2020) MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibi-tors. International Journal of Molecular Sciences, 21, 4544.
https://doi.org/10.3390/ijms21124544
[40]  Henriksen, M., Johnsen, K.B., Andersen, H.H., Pilgaard, L. and Duroux, M. (2014) MicroRNA Expression Signatures Determine Prognosis and Survival in Glioblastoma Multiforme—A Systematic Overview. Molecular Neurobiology, 50, 896-913.
https://doi.org/10.1007/s12035-014-8668-y
[41]  He, H., Wang, L., Zhou, W., et al. (2015) MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs. PLoS ONE, 10, e0125672.
https://doi.org/10.1371/journal.pone.0125672
[42]  Liu, H., Sun, Y., Tian, H., et al. (2019) Characterization of Long Non-Coding RNA and Messenger RNA Profiles in Laryngeal Cancer by Weighted Gene Co-Expression Network Anal-ysis. Aging (Albany NY), 11, 10074-10099.
https://doi.org/10.18632/aging.102419
[43]  Roman-Canal, B., Tarragona, J., Moiola, C.P., et al. (2019) EV-Associated miRNAs from Peritoneal Lavage as Potential Diagnostic Biomarkers in Colorectal Cancer. Journal of Translational Medicine, 17, 208.
https://doi.org/10.1186/s12967-019-1954-8
[44]  Gilbertson, R.J. and Clifford, S.C. (2003) PDGFRB Is Overex-pressed in Metastatic Medulloblastoma. Nature Genetics, 35, 197-198.
https://doi.org/10.1038/ng1103-197
[45]  Young, L.C. and Rodriguez-Viciana, P. (2018) MRAS: A Close but Un-derstudied Member of the RAS Family. Cold Spring Harbor Perspectives in Medicine, 8, a033621.
https://doi.org/10.1101/cshperspect.a033621
[46]  Omazic, B., Ayoglu, B., L？hr, M., et al. (2017) A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients with Pancreatic Cancer. Journal of Immunotherapy, 40, 132-139.
https://doi.org/10.1097/CJI.0000000000000164
[47]  Zhu, J., Zhao, Y.P. and Zhang, Y.Q. (2020) Low Expression of FOSL1 Is Associated with Favorable Prognosis and Sensitivity to Radiation/Pharmaceutical Therapy in Lower Grade Glioma. Neurological Research, 42, 522-527.
https://doi.org/10.1080/01616412.2020.1748323
[48]  Zhang, M., Liang, L., He, J., et al. (2020) Fra-1 Inhibits Cell Growth and the Warburg Effect in Cervical Cancer Cells via STAT1 Regulation of the p53 Signaling Pathway. Frontiers in Cell and Developmental Biology, 8, Article ID: 579629.
https://doi.org/10.3389/fcell.2020.579629
[49]  Oguri, T., Katoh, O., Takahashi, T., et al. (1998) The Krüppel-Type Zinc Finger Family Gene, HKR1, Is Induced in Lung Cancer by Exposure to Platinum Drugs. Gene, 222, 61-67.
https://doi.org/10.1016/S0378-1119(98)00464-8
[50]  Chua-On, D., Proungvitaya, T., Tummanatsakun, D., et al. (2020) Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients. Biomolecules, 10, 1021.
https://doi.org/10.3390/biom10071021
[51]  Li, J., Zhang, C., Yuan, X., Ren, Z. and Yu, Z. (2020) Correlations between Stemness Indices for Hepatocellular Carcinoma, Clinical Characteristics, and Prognosis. American Journal of Translational Research, 12, 5496-5510.
[52]  Wang, K., Chai, L., Qiu, Z., Zhang, Y., Gao, H. and Zhang, X. (2019) Overexpression of TRIM26 Suppresses the Proliferation, Metastasis, and Glycolysis in Papillary Thyroid Carcinoma Cells. Journal of Cellular Physiology, 234, 19019-19027.
https://doi.org/10.1002/jcp.28541
[53]  Takaji, M., Ko-matsu, Y., Watakabe, A., Hashikawa, T. and Yamamori, T. (2009) Paraneoplastic Antigen-Like 5 Gene (PNMA5) Is Preferentially Expressed in the Association Areas in a Primate Specific Manner. Cerebral Cortex, 19, 2865-2879.
https://doi.org/10.1093/cercor/bhp062
[54]  Wang, T., Xuan, Z., Dou, Y., et al. (2019) Identification of Novel Mu-tations in Preaxial Polydactyly Patients through Whole-Exome Sequencing. Molecular Genetics & Genomic Medicine, 7, e690.
https://doi.org/10.1002/mgg3.690
[55]  Li, C., Yuan, B., Yu, X., et al. (2020) SLC19A1 May Serve as a Po-tential Biomarker for Diagnosis and Prognosis in Osteosarcoma. Clinical Laboratory, 66.
https://doi.org/10.7754/Clin.Lab.2020.200246
[56]  Wallmann, T., Zhang, X.M., Wallerius, M., et al. (2018) Mi-croglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity. iScience, 9, 71-83.
https://doi.org/10.1016/j.isci.2018.10.011
[57]  Miao, L., Yin, R.X., Zhang, Q.H., et al. (2019) A Novel circR-NA-miRNA-mRNA Network Identifies circ-YOD1 as a Biomarker for Coronary Artery Disease. Scientific Reports, 9, Article No. 18314.
https://doi.org/10.1038/s41598-019-54603-2

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